This project is designed to investigate several novel aspects of the anatomical organization and pathology of the cerebral cortex which are directly relevant to cognitive functions. The issues addressed here follow directly on questions raised in other projects of this Program, especially on those pertaining to the neural basis of memory. The research is aimed at providing neuroanatomical characterizations of: (a) connectional links within specified cortical systems, and (b) the intrinsic structure of cortical regions participating in these systems. Such information is critical for the interpretation of experimental results based on any of the currently available approaches to the neurological basis of cognition in humans (e.g. the lesion method, PET, electrophysiology), and for the continued evaluation of theoretical formulations regarding the neural architecture and operations that may subserve cognition in primates. The proposal is divided into three subprojects: (1) high resolution tracing of connections from the parahippocampal cortex in monkeys, (2) topography of the human perforant pathway, and (3) modular organization of the human entorhinal cortex. Each subproject is based on a combination of modern histo- and immunocytochemical methods and conventional histology, to permit the dissection of chemically identified neurons and/or neurites. The information obtained from these tightly interrelated projects will contribute to a better understanding of the substrates of both normal and disordered human cognition at the cellular and connectional levels, and to a characterization of their alteration in conditions such as Alzheimer's disease.